There are intimate interconnections between the central and peripheral nervous systems and the immune system through overlapping expression of regulatory mediators and receptors. Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites where it can acti to modulate inflammation. Local CRH expression parallels the severity of inflammation in animal models of arthritis and in patients with rheumatoid arthritis. We hypothesis that CRH affects local immune and inflammatory processes in synovial tissues. We will characterize CRH receptors of synoviocytes, explore mechanisms by which CRH exerts modulatory effects on the inflammatory process by analysis of inflammatory mediator production after treeatment with CRH, exmine regulation of peripheral nervous system CRH expression during inflammation, and evaluated the importance of CRH in inflammatory arthritis using the antigen-induced arthritis model in Lewis rats.